Water → (R)-N-(4-Cyano-2-methylphenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydro-isoquinoline-2(1H)-carboxamide

HRID 445338Notes

Reaction equation

HRID 445338 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:10].[H-].[Na+].[F:13][C:14]([F:44])([F:43])[C:15]1[CH:20]=[CH:19][C:18]([C@@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24][CH2:23][N:22]2[C:31](OC2C=CC([N+]([O-])=O)=CC=2)=[O:32])=[CH:17][CH:16]=1.O>C1COCC1>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:1][C:31]([N:22]2[CH2:23][CH2:24][C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C@H:21]2[C:18]2[CH:19]=[CH:20][C:15]([C:14]([F:43])([F:13])[F:44])=[CH:16][CH:17]=2)=[O:32])=[C:3]([CH3:10])[CH:4]=1)#[N:7]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 70103164-Amino-3-methylbenzonitrileHCID 59536297(R)-4-Nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 59536288(R)-N-(4-Cyano-2-methylphenyl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydro-isoquinoline-2(1H)-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-amino-3-methylbenzonitrile (30 mg, 226 μmol) in THF (2 mL) was added sodium hydride, 60% dispersion in mineral oil (15 μL, 339 pimp. The resulting mixture was then stirred at RT for 2 min. Then, (R)-4-nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (100 mg, 226 μmol, example 88) was added and the mixture was stirred at RT for overnight. Then, 26 mg of NaH (60% dispersion in mineral oil) was added and the mixture was stirred at RT for overnight. Then, H2O (0.2 mL) was added and the solvents were removed. The residue was then dissolved in a solution of DMSO and MeOH (1:1, 1.0 mL). The solution was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the desired product, which was dissolved in MeOH (1.0 mL). The solution was then washed through PL-HCO3 MP resin (polymerlabs, 200 mg/6 mL tube) and the resin was then washed with MeOH (2×0.5 mL). The combined washings were then concentrated and dried under vacuum to give the title compound as a yellow solid. MS (ESI, positive ion) m/z: 436 (M+H).

Workup

  1. stirringthe mixture was stirred at RT for overnight
  2. stirringthe mixture was stirred at RT for overnight
  3. customthe solvents were removed
  4. dissolutionThe residue was then dissolved in a solution of DMSO and MeOH (1:1, 1.0 mL)
  5. customThe solution was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Sources & evidence

ORD record
ord-94f67bb983ff478cba0de85ce7f82b5c
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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